Senescent cells harbour features of the cancer epigenome
| Autor: | Greg Donahue, John van Tuyn, Nathan D. VanderKraats, Peter D. Adams, Tony McBryan, Shelley L. Berger, Parisha P. Shah, Donncha S. Dunican, Richard R. Meehan, Mark E. Drotar, Taranjit Singh Rai, John R. Edwards, David M. Nelson, Hazel A Cruickshanks, Claire Brock |
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| Rok vydání: | 2013 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Bisulfite sequencing Gene Expression Cell Cycle Proteins Nerve Tissue Proteins Biology DNA methyltransferase Article Cell Line Epigenesis Genetic Epigenetics of physical exercise Neoplasms Basic Helix-Loop-Helix Transcription Factors Humans DNA (Cytosine-5-)-Methyltransferases Cancer epigenetics Promoter Regions Genetic RNA-Directed DNA Methylation Cellular Senescence Genome Human Cell Biology DNA Methylation Cell biology Protein Transport DNA methylation Cancer cell CpG Islands DNA hypomethylation |
| Zdroj: | Nature Cell Biology. 15:1495-1506 |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, late-replicating, lamin-associated domains and is linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence. Low-level gains of methylation are enriched in CpG islands, including at genes whose methylation and silencing is thought to promote cancer. Gains and losses of methylation in replicative senescence are thus qualitatively similar to those in cancer, and this ‘reprogrammed’ methylation landscape is largely retained when cells bypass senescence. Consequently, the DNA methylome of senescent cells might promote malignancy, if these cells escape the proliferative barrier. Cancer is associated with altered DNA methylation. Using whole-genome single-nucleotide sequencing, Adams and colleagues reveal that senescent cells, as well as cells that have bypassed senescence through p53 and pRB inactivation, exhibit methylation changes similar to those seen in cancer. |
| Databáze: | OpenAIRE |
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